Dietary Intervention and Intestinal Microbiota in Non-alcoholic Fatty Liver

This study is currently recruiting participants.
Verified January 2014 by University Hospital, Geneva
Sponsor:
Information provided by (Responsible Party):
Prof. Claude Pichard, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01477307
First received: November 15, 2011
Last updated: January 1, 2014
Last verified: January 2014

November 15, 2011
January 1, 2014
July 2011
December 2014   (final data collection date for primary outcome measure)
abundance of fecal abundance of fecal Bacteroidetes [ Time Frame: thrice, at inclusion, day 21 and day 42 ] [ Designated as safety issue: No ]
Bacterial cells/g caecal content
abundance of fecal abundance of fecal Bacteroidetes [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
To assess the impact of dietary intervention on the relative abundance of fecal Bacteroidetes (expressed as the bacteroidetes to firmicutes ratio) in patients with obesity, abnormal liver function tests and NAFLD
Complete list of historical versions of study NCT01477307 on ClinicalTrials.gov Archive Site
  • liver fat content [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    picsel/uni MRI
  • liver function tests [ Time Frame: four times, at screening, inclusion, day 21 and day 42 ] [ Designated as safety issue: No ]
    mmol/l
  • CRP [ Time Frame: thrice, at screening, inclusion and day 21 ] [ Designated as safety issue: No ]
    mg/l
  • serum cytokines [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    ng/ml
  • serum LPS [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    pg/ml
  • Breath test pullulation [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
  • intestinal permeability [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    Polyethylene glycol 3350/Polyethylene glycol 400 ratio
  • body composition [ Time Frame: thrice, at inclusion, day 21 and day 42 ] [ Designated as safety issue: No ]
    body composition in kg and % of body weight
  • liver lipid composition (biopsy) [ Time Frame: once, at screening ] [ Designated as safety issue: No ]
  • liver fat content [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    picsel/uni MRI
  • liver function tests [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    mmol/l
  • CRP [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    mg/l
Not Provided
Not Provided
 
Dietary Intervention and Intestinal Microbiota in Non-alcoholic Fatty Liver
Effect of Dietary Intervention on Intestinal Microbiota in Patients With Non-alcoholic Fatty Liver Disease

In patients with NAFLD/NASH, changes in liver lipid composition and function tests following a short dietary intervention are associated with changes in gut microbiota

Study Hypothesis: In patients with NAFLD/NASH, changes in liver lipid composition and function tests following a short dietary intervention are associated with changes in gut microbiota

Study period:

  • Study duration for the participant: 7-10 weeks (1-4 weeks screening period, 3 weeks of intervention + 3 weeks of follow-up)
  • Expected study completion date: 30.04.2012 Study type: Single arm before-after study

Number of patients:

20 subjects with obesity and NAFLD / NASH

Main criteria for inclusion:

  • Obesity defined as BMI>30
  • Abnormal liver function tests defined as ALT > 1.5 times the upper limit of normal
  • NAFLD present at liver biopsy
  • Age > 18 years, < 60 years

Main exclusion criteria:

  • Inability or unwillingness to give consent
  • Parenteral nutrition or other ongoing dietary intervention
  • Bulimia
  • Other known cause of chronic liver disease, including hepatitis B or C, iron overload,
  • Use of substances known to alter intestinal permeability, including alcohol and NSAIDs

Intervention:

The phase 2 Eurodiet® program will be used as standardized hypo-caloric diet during a 3-weeks intervention period. The products are commercially available and prescribed to reach 1000 kcal/day. These products will be offered free of charge.

Primary Objective:

To assess the impact of dietary intervention on the relative abundance of fecal Bacteroidetes (expressed as the bacteroidetes to firmicutes ratio) in patients with obesity, abnormal liver function tests and NAFLD

Secondary Objectives:

  1. To compare fecal microbiota from patients with NAFLD or NASH at baseline
  2. To assess fecal microbiota changes in patients with NAFLD or NASH after dietary intervention
  3. To measure liver fat content at baseline and after dietary intervention
  4. To assess changes in liver function tests and ultrasensitive CRP, cytokines and serum LPS in relation to changes in microbiota and liver lipid composition
  5. To measure orocecal transit time, an index of intestinal pullulation, at baseline and after dietary intervention in patients with NAFLD or NASH
  6. To measure intestinal permeability at baseline and after dietary intervention in patients with NAFLD or NASH
  7. To assess body composition changes in relation to changes in microbiota and liver lipid composition

Statistical methods:

Baseline and end-of-treatment changes for both bacterial genders and subspecies will be compared using paired-sample Wilcoxon signed-rank test. ANOVA and paired t-test for comparison of other changes within groups. Pearson or Spearman tests will be used to assess correlations between changes in microbiota and changes in liver fat content, liver function tests, CRP, cytokines and intestinal pullulation and permeability.

Sample size:

20 patients with NAFLD/NASH will be studied before and after dietary intervention.

Assessment of end-points:

Fecal microbiota will be analysed with 454-Flex metagenomics Ultrasensitive CRP and serum LPS changes as compared with baseline Serum cytokines as measured with ELISA Liver fat content and composition will be measured using MR spectroscopy Small intestinal overgrowth and intestinal permeability will be assessed using standard 13C breath tests and polyethyleneglycol absorption test Body mass composition changes will be assessed using bioelectrical impedance analysis

Safety :

All adverse events will be recorded throughout the study, in compliance with GCP ICH E6 and national regulations.

Observational
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

Obesity defined as BMI>30 Abnormal liver function tests defined as ALT > 1.5 times the upper limit of normal NAFLD present at liver biopsy Age > 18 years, < 60 years

  • Obesity
  • Non-alcoholic Fatty Liver Disease (NAFLD)
Other: Hypocaloric diet
Eurodiet,standardized hypo-caloric diet, during 3 weeks
Other Name: eurodiet 2
hypocaloric diet
The included patients are assigned to a hypocaloric standardized diet for 3 weeks.
Intervention: Other: Hypocaloric diet
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
June 2015
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

Obesity defined as BMI>30 Abnormal liver function tests defined as ALT > 1.5 times the upper limit of normal NAFLD present at liver biopsy Age > 18 years, < 60 years

Exclusion Criteria:

Inability or unwillingness to give consent Bulimia Other known cause of chronic liver disease, including hepatitis B or C, iron overload, Use of substances known to alter intestinal permeability, including alcohol and NSAIDs

Both
18 Years to 60 Years
Yes
Contact: Claude Pichard, MD,PhD +41 22 37 29 349 claude.pichard@unige.ch
Contact: Zoltan Patakay, MD +41 79 58 290 Zoltan.Pataky@hcuge.ch
Switzerland
 
NCT01477307
10-231
Yes
Prof. Claude Pichard, University Hospital, Geneva
University Hospital, Geneva
Not Provided
Principal Investigator: Claude Pichard, MD Geneva University Hospital
University Hospital, Geneva
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP